Outcome of patients with splanchnic venous thrombosis presenting without overt MPN: A role for the JAK2 V617F mutation re-evaluation

Introduction

Although investigation for JAK2 V617F mutation is recommended in patients presenting with splanchnic venous thrombosis (SVT), no specific clinical advice is given to SVT patients presenting without myeloproliferative neoplasms (MPN) and JAK2 V617F mutation. In MPN-free SVT patients, to investigate the clinical outcome, the clinical impact of re-evaluation for the JAK2 V617F mutation, and relationships with the occurrence and time to diagnosis of MPN.

Materials and Methods

A cohort of non-cirrhotic SVT patients, enrolled at a single centre and prospectively analyzed.

Results

In 121 SVT patients prospectively followed from 1994 to 2012, a MPN was present in 28 (23.1%). Additional 13 patients (10.7%) showed only the JAK2 V617F mutation. During the follow-up, the JAK2 V617F mutation and/or MPN were identified in 8 patients (median time of development: 21 months, range 6-120), whereas 72 remained (MPN and JAK2 V617F)-free until the end of the observation.The mortality rate was higher among patients presenting with MPN and/or the JAK2 V617F mutation than in patients who developed later or remained disease-free (p = 0.032). The thrombosis-free survival was lower in patients with (p = 0.04) or developing later MPN and the JAK2 V617F mutation (p = 0.005) than in patients (MPN and JAK2 V617F)-free. The incidence of bleeding was similar among groups.

Conclusions

MPN with or without circulating positive clones for JAK2 V617F mutation can occur long after a SVT, identifying at risk patients for new thrombotic events. If confirmed in other studies, re-evaluation for JAK2 V617F mutation may be of help in early MPN detection and clinical management of SVT patients.     

Ultrasound diagnosis of bony nerve entrapment: Case series and literature review

Introduction: Nerve entrapment due to osseous callus formation is a rare complication after bone fracture. Electrodiagnostic studies and routine radiographic imaging often fail to demonstrate the pathology. The diagnosis is difficult and is often made incidentally upon surgical exploration. Nerve ultrasonography has not been used routinely to assess such lesions. Methods: We report 5 cases of nerve entrapment in osseous callus after fractures that occurred in 2011 and 2012. The diagnosis was made by ultrasound (US). We then performed a review of the relevant literature. Conclusions: US is becoming an invaluable tool for diagnosing peripheral nerve entrapments. The current cases suggest that nerve US should be strongly considered as an adjunctive diagnostic tool for nerve palsies developing after trauma. Muscle Nerve 48 : 445–450, 2013     

Neurogenesis in temporal lobe epilepsy: Relationship between histological findings and changes in dentate gyrus proliferative properties

Objective

The relationship between hippocampal histopathological abnormalities, epileptogenesis and neurogenesis remains rather unclear.

Methods

Tissue samples including the subgranular zone of dentate gyrus (DG) were freshly collected for tissue culture for neurospheres generation in 16 patients who underwent surgery for drug-resistant temporal lobe epilepsy. Remaining tissues were histologically examined to assess the presence of mesial temporal sclerosis (MTS) and focal cortical dysplasia.

Results

MTS was detected in 8 cases. Neurospheres were formed in 10/16 cases. Only three out of these 10 cases exhibited MTS; on the contrary 5/6 cases lacking neurosphere proliferation presented MTS. There was a significant correlation between presence of MTS and absence of proliferation (p = 0.0389). We also observed a correlation between history of febrile seizures (FS) and presence of MTS (p = 0.0004) and among the 6 cases lacking neurosphere proliferation, 4 cases (66.6%) had experienced prolonged FS. Among “proliferating” cases the percentage of granular cells pathology (GCP) was lower (20% vs 50%) compared to “non proliferating” cases.

Conclusion

A decreased potential to generate neurosphere from the SGZ is related to MTS and to alterations of dentate gyrus granule cells, especially in MTS type 1b and GCP type 1. These histological findings may have different prognostic implications, regarding seizure and neuropsychological outcome, compared to patients with other epileptogenic lesions (such as FCD, glioneuronal tumours, vascular lesions).     

Mental health and social participation skills of wheelchair basketball players: A controlled study

The aim of this study was to assess differences in psychological well-being, symptomatic psychological disorders and social participation, between competitive wheelchair basketball participants and those non-participants. Forty-six wheelchair participants, 24 Basketball players (aged 35.60 ± 7.56) and 22 non-players (aged 36.20 ± 6.23), completed three validated self-report questionnaires: Participation Scale (PS), Psychological Well-Being Scale [PWBS] and Symptom Checklist 90 R [SCL-90-R]. ANOVA showed significant overall differences between the two groups. The social restriction score, evaluated by PS, was significantly higher in the non-basketball participants (p = 0.00001) than the basketball participants. The PWB Scale showed significant differences in all 6 dimensions: positive relations with others, environmental mastery, personal growth, purpose in life and self-acceptance (p < 0.01), and autonomy (p < 0.05), with better scores in the basketball participants. The SCL-90-R scores were significantly lower for the basketball group in the following 6 symptomatic dimensions: depression, phobic anxiety, and sleep disorder (p < 0.01), somatization, interpersonal sensitivity and psychoticism (with p < 0.05). It was concluded that competitive wheelchair basketball participants showed better psychological well-being and social skills than those non-participants.     

UDP‐glucose enhances outward K+ currents necessary for cell differentiation and stimulates cell migration by activating the GPR17 receptor in oligodendrocyte precursors

In the developing and mature central nervous system, NG2 expressing cells comprise a population of cycling oligodendrocyte progenitor cells (OPCs) that differentiate into mature, myelinating oligodendrocytes (OLGs). OPCs are also characterized by high motility and respond to injury by migrating into the lesioned area to support remyelination. K⁺ currents in OPCs are developmentally regulated during differentiation. However, the mechanisms regulating these currents at different stages of oligodendrocyte lineage are poorly understood. Here we show that, in cultured primary OPCs, the purinergic G‐protein coupled receptor GPR17, that has recently emerged as a key player in oligodendrogliogenesis, crucially regulates K⁺ currents. Specifically, receptor stimulation by its agonist UDP‐glucose enhances delayed rectifier K⁺ currents without affecting transient K⁺ conductances. This effect was observed in a subpopulation of OPCs and immature pre‐OLGs whereas it was absent in mature OLGs, in line with GPR17 expression, that peaks at intermediate phases of oligodendrocyte differentiation and is thereafter downregulated to allow terminal maturation. The effect of UDP‐glucose on K⁺ currents is concentration‐dependent, blocked by the GPR17 antagonists MRS2179 and cangrelor, and sensitive to the K⁺ channel blocker tetraethyl‐ammonium, which also inhibits oligodendrocyte maturation. We propose that stimulation of K⁺ currents is responsible for GPR17‐induced oligodendrocyte differentiation. Moreover, we demonstrate, for the first time, that GPR17 activation stimulates OPC migration, suggesting an important role for this receptor after brain injury. Our data indicate that modulation of GPR17 may represent a strategy to potentiate the post‐traumatic response of OPCs under demyelinating conditions, such as multiple sclerosis, stroke, and brain trauma.     

Peri-implant collagen fibers around human cone Morse connection implants under polarized light: a report of three cases

Most of the histologic studies found in the literature on the peri-implant soft tissues have been done in animals and usually have been confined to mandibular implants fitted with healing or standard abutments. Few studies have investigated human peri-implant soft tissues. Moreover, the structure and dimensions of the peri-implant soft tissues in immediately loaded implants have not been investigated in depth. Human histologic data are valuable to validate animal models. This histologic and histomorphometric study evaluated the peri-implant soft tissues around three immediately loaded implants in humans. The implants were retrieved using a trephine and treated to obtain thin, ground sections. The sulcular epithelium was composed of approximately four to five layers of parakeratinized epithelial cells and had a length of approximately 1.2 to 1.3 mm. The junctional epithelium was composed of approximately three to four layers of epithelial cells and had a length of approximately 1.0 to 1.5 mm. Connective tissue attachment had a width of between 400 and 800 μm. Peri-implant collagen fibers, in the form of bundles (1- to 5-μm thick), began at the crestal bone and were oriented perpendicular to the abutment surface until 200 μm from the surface, where they became parallel running in several directions. Collagen fibers appeared to form a three-dimensional network around the abutment. No acute or chronic inflammatory cell infiltrate was present. Collagen fibers oriented in a perpendicular manner and in direct contact with the abutment surface were not observed in any of the specimens. This differentiated network of fibers may have clinical relevance as a mechanical protection of the underlying bone. These human histologic data are extremely valuable to validate and confirm those obtained from studies performed on animal models. Moreover, immediate loading of the implants did not compromise soft tissue integration.     

Histologic and histomorphometric evaluation of an implant retrieved 8 years after insertion in a sinus augmented with anorganic bovine bone and anorganic bovine matrix associated with a cell-binding peptide: a case report

Few histologic and histomorphometric reports are present in the literature regarding the peri-implant bone response around implants inserted in sinuses grafted with different biomaterials. Anorganic bovine bone (ABB) and anorganic bovine matrix with the addition of an active cell-binding peptide (PepGen P-15) are xenogenic materials that have been reported to present biocompatibility and osteoconductivity. A monolateral sinus augmentation procedure with ABB (50%) and PepGen P-15 (50%) was performed in a 54-year-old man. Two titanium implants with a sandblasted and acid-etched surface were inserted after 6 months. After an additional 6 months, a fixed prosthetic restoration was fabricated. One implant fractured in the coronal portion after an 8-year loading period and was removed using a 5-mm trephine bur. Few particles of both grafting materials were present in the peri-implant bone. No graft material particles were found in contact with the implant surface, and bone was always interposed between the graft materials and surface. No inflammatory cell infiltrate, multinucleated giant cells, or foreign body reaction cells were found. The tissues around the implant were composed of 51.4% ± 4.8% bone, 6.2% ± 0.7% ABB particles, 2.4% ± 0.5% PepGen P-15, and 40.0% ± 7.1% marrow spaces. The bone-implant contact percentage was 78.4% ± 4.1%. A sinus augmentation procedure using ABB and PepGen P-15 produced bone formation with subsequent implant osseointegration, which was still present after 8 years of implant loading.